Development of Aspergillus protease with ovalbumin-induced allergic chronic rhinosinusitis model in the mouse

Background: Chronic rhinosinusitis (CRS) is a multifactorial inflammatory disease. Particularly, eosinophilic CRS is often recalcitrant to treatment, so an appropriate animal model is required to evaluate the pathogenesis of, and to develop therapies for, recalcitrant eosinophilic CRS. This study aimed to improve the ovalbumin (OVA)-induced mouse model of eosinophilic/allergic CRS by combining OVA with Aspergillus protease, which is known to trigger allergic reactions in mouse lungs. Methods: In a model of allergic CRS, mice were challenged intranasally with Aspergillus protease combined with OVA. Local and systemic responses were measured. Protease (0.54 U) from Aspergillus oryzae, prepared with or without OVA (75 micrograms), OVA alone, or saline, was administered intranasally to wild-type mice for 5 weeks. Sinonasal complex samples were evaluated histologically, and interleukin (IL)-4, IL-5, IL-6, macrophage inflammatory protein (MIP) 2, and tumor necrosis factor (TNF) alpha were measured in nasal lavage fluid. A differential white blood cell count was also performed. Results: OVA alone induced minimal eosinophilic inflammation in sinonasal mucosa, while protease + OVA and protease alone induced moderate eosinophilic inflammation. Protease + OVA elevated eosinophil counts in blood comparable with controls, but not compared with OVA alone. Although IL-4, IL-5, IL-6, MIP-2, and TNF-alpha were increased in all study mice, the levels of IL-4 and IL-6 were higher in mice treated with protease + OVA than in mice treated with OVA alone. Protease alone excessively elevated the levels of IL-6, MIP-2, and TNF-alpha, not Th2 cytokines, compared with OVA alone and protease + OVA. Conclusion: Aspergillus protease combined with OVA induced more severe allergic inflammation in sinonasal mucosa compared with OVA alone and similar eosinophilia. This model could be more relevant to recalcitrant eosinophilic CRS in humans than OVA-induced allergic CRS.